In primary open angle glaucoma there is an increase in the outflow resistance in the chamber angle that seems to be due to a reduction in the number of routes between the anterior chamber and Schlemm's canal and increased narrowness of these routes. Accumulation of extracellular material between the trabecular beams is one of the factors involved and may reduce also the conductance of the uveoscleral outflow routes. As a result of the rise in outflow resistance there is a pressure rise in the eye that tends to damage the optic nerve head. The rise in pressure that the eye can tolerate varies greatly; glaucomatous damage of the optic nerve head can be observed even at intraocular pressures that are regarded as normal. Our studies aim at finding means by which material clogging the outflow routes can be dissolved and/or washed out from the chamber angle. Another goal is to find means by which the rate of aqueous formation and the drainage through different routes can be adjusted at levels resulting in an intraocular pressure that can be tolerated by the eye. A third goal is to elucidate the mechanism by which the high intraocular pressure tends to damage the optic nerve head. Our plan is to analyze the way in which alpha-chymotrypsin and Na2EDTA reduce the resistance in the outflow routes. A cast technique is used to study the three-dimensional arrangement of the routes. The effects on effective pore sizes in different parts of the routes are analyzed in experiments with perfusion of different sized particles. The roles of dopamine, substance P, vasoactive intestinal polypeptide, thyrotropin releasing hormone, and neuropeptide Y on the formation of aqueous humor and the drainage via Schlemm's canal and that via uveoscleral routes will be studied with an isotope dilution method. Radioactively labeled albumin is perfused through the anterior chamber and the rate of saqueous inflow calculated from the dilution data. The outflow into the general circulation is calculated from the rise in plasma activity and outflow through uveoscleral routes is calculated as the difference: inflow - outflow to the general circulation. The C14-deoxyglucose method of Sololoff is used to reveal if experimental chronic glaucoma causes damage to the optic nerve head by causing partial ischemia with anaerobic glycolysis in the optic nerve head region. Experiments are planned also to see if recurrent episodes with high intraocular pressure tend to cause a distension of the lamina cribrosa which increases the pressure sensitivity of the lamina and the retrolaminar regions.